title: N-Alkyl dien- and trienamides from the roots of Otanthus maritimus with binding affinity for opioid and cannabinoid receptors.
abstract: Two new thienylheptatrienamides (1, 5) and one new neo-lignan (12), together with thirteen known compounds (2, 3, 4, 6-11, 13-16) were isolated from the roots of Otanthus maritimus. The structures of the new compounds were elucidated on the basis of extensive 1D and 2D NMR experiments as well as high resolution mass spectrometry. All the isolated amides (1-10), the known pontica epoxide (11) and the new neo-lignan (12) were evaluated for their binding affinity to the CB1 and CB2 as well as to the μ and δ opioid receptors. Some alkylamides showed moderately high binding affinity for CB2 receptors and 1-[(2E,4E,8Z)-tetradecatrienoyl]piperidine (10) resulted the most active one with a Ki value of 160 nM. As far as we know, this is the first example of a tertiary alkylamide that binds CB2 receptors with significant potency. Compounds that showed the highest affinity for cannabinoid receptors (6-8, 10) were much less potent against opioid receptors. Primary structure-activity relationship is discussed. Docking experiments were carried out with the aim to understand the key interactions of the most active compounds with CB2 receptor.
authors.affiliation: Institute of Translational Pharmacology, UOS of Cagliari, National Research Council, Parco Scientifico e Tecnologico-Pula, Cagliari, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ruiu
authors.forename: Nicola
authors.initials: N
authors.lastname: Anzani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Orrù
authors.forename: Costantino
authors.initials: C
authors.lastname: Floris
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Caboni
authors.forename: Elias
authors.initials: E
authors.lastname: Maccioni
authors.forename: Simona
authors.initials: S
authors.lastname: Distinto
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Filippo
authors.initials: F
authors.lastname: Cottiglia
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D019659:Asteraceae / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D017705:Lignans / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D010421:Pentanoic Acids / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000577:Amides; D017705:Lignans; D010421:Pentanoic Acids; D043882:Receptors, Cannabinoid; D011957:Receptors, Opioid; D013876:Thiophenes
keywords: Alkylamides; Cannabinoid receptors; Molecular modeling; NMR; Opioid receptors; Otanthus maritimus